The main goal of this project is to test and extend hypotheses regarding the neural systems and mechanisms involved in age-related memory decline. The project combines neurochemical and behavioral methods used with rats. Research on neural systems will focus on the hippocampal formation and the dorsal neostriatum, both of which are implicated in age-related neurodegeneration and in behaviorally dissociable forms of memory. Research on neural mechanisms will focus on age-related pre- and posttranslational changes in protein kinase C (PKC) isozymes. Specific Aims are these: (1) Examine the relationship between PKC and age-related impairment of memory formation. Learning-induced and age-related alterations in PKC isozymes will be examined using in situ hybridization and radioenzymatic assay techniques. (2) Examine age-related changes in cholinergic integrity in the hippocampal formation and the dorsal neostriatum using neurochemical analyses, and test for correlations with behavioral measures. (3) Develop a behavioral analysis with multiple and dissociable mnemonic components that is sensitive to the effects of aging and to the integrity of the hippocampal formation and the dorsal neostriatum. This proposal, aimed at identifying mechanisms and brain regions involved in age-related memory decline, may provide a base for development of treatment strategies and therapeutics.